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Novel genetic variant in FTO influences insulin levels and insulin resistance in severely obese children and adolescents

Jacobsson, J. A.; Klovins, J.; Kapa, I.; Danielsson, P.; Svensson, V.; Ridderstråle, Martin LU ; Gyllensten, U.; Marcus, C.; Fredriksson, R. and Schioth, H. B. (2008) In International Journal of Obesity 32(11). p.1730-1735
Abstract
Background: The global prevalence of obesity and overweight is increasing rapidly among adults as well as among children and adolescents. Recent genome-wide association studies have provided strong support for association between variants in the FTO gene and obesity. We sequenced regions of the FTO gene to identify novel variants that are associated with obesity and related metabolic traits. Results: We screened exons 3 and 4 including exon-intron boundaries in FTO in 48 obese children and adolescents and identified three novel single nucleotide polymorphism in the fourth intronic region, (c.896 + 37A > G, c.896 + 117C > G and c.896 + 223A > G). We further genotyped c.896 + 223A > G in 962 subjects, 450 well-characterized obese... (More)
Background: The global prevalence of obesity and overweight is increasing rapidly among adults as well as among children and adolescents. Recent genome-wide association studies have provided strong support for association between variants in the FTO gene and obesity. We sequenced regions of the FTO gene to identify novel variants that are associated with obesity and related metabolic traits. Results: We screened exons 3 and 4 including exon-intron boundaries in FTO in 48 obese children and adolescents and identified three novel single nucleotide polymorphism in the fourth intronic region, (c.896 + 37A > G, c.896 + 117C > G and c.896 + 223A > G). We further genotyped c.896 + 223A > G in 962 subjects, 450 well-characterized obese children andadolescents and 512 adolescents with normal weight. Evidence for differences in genotype frequencies were not detected for the c.896 + 223A > G variant between extremely obese children and adolescents and normal weight adolescents (P = 0.406, OR = 1.154 (0.768-1.736)). Obese subjects with the GG genotype, however, had 30% increased fasting serum insulin levels (P = 0.017) and increased degree of insulin resistance (P = 0.025). There were in addition no differences in body mass index (BMI) or BMI standard deviation score (SDS) levels among the obese subjects according to genotype and the associations with insulin levels and insulin resistance remained significant when adjusting for BMI SDS. Conclusion: These findings suggest that this novel variant in FTO is affecting metabolic phenotypes such as insulin resistance, which are not mediated through differences in BMI levels. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
adolescents, children, metabolic phenotypes, FTO, polymorphism
in
International Journal of Obesity
volume
32
issue
11
pages
1730 - 1735
publisher
Nature Publishing Group
external identifiers
  • wos:000260925300019
  • scopus:56549107150
ISSN
1476-5497
DOI
10.1038/ijo.2008.168
language
English
LU publication?
yes
id
4453002d-9175-4585-8998-7149cd07d6d6 (old id 1308670)
date added to LUP
2009-03-19 09:30:17
date last changed
2017-08-27 03:58:46
@article{4453002d-9175-4585-8998-7149cd07d6d6,
  abstract     = {Background: The global prevalence of obesity and overweight is increasing rapidly among adults as well as among children and adolescents. Recent genome-wide association studies have provided strong support for association between variants in the FTO gene and obesity. We sequenced regions of the FTO gene to identify novel variants that are associated with obesity and related metabolic traits. Results: We screened exons 3 and 4 including exon-intron boundaries in FTO in 48 obese children and adolescents and identified three novel single nucleotide polymorphism in the fourth intronic region, (c.896 + 37A > G, c.896 + 117C > G and c.896 + 223A > G). We further genotyped c.896 + 223A > G in 962 subjects, 450 well-characterized obese children andadolescents and 512 adolescents with normal weight. Evidence for differences in genotype frequencies were not detected for the c.896 + 223A > G variant between extremely obese children and adolescents and normal weight adolescents (P = 0.406, OR = 1.154 (0.768-1.736)). Obese subjects with the GG genotype, however, had 30% increased fasting serum insulin levels (P = 0.017) and increased degree of insulin resistance (P = 0.025). There were in addition no differences in body mass index (BMI) or BMI standard deviation score (SDS) levels among the obese subjects according to genotype and the associations with insulin levels and insulin resistance remained significant when adjusting for BMI SDS. Conclusion: These findings suggest that this novel variant in FTO is affecting metabolic phenotypes such as insulin resistance, which are not mediated through differences in BMI levels.},
  author       = {Jacobsson, J. A. and Klovins, J. and Kapa, I. and Danielsson, P. and Svensson, V. and Ridderstråle, Martin and Gyllensten, U. and Marcus, C. and Fredriksson, R. and Schioth, H. B.},
  issn         = {1476-5497},
  keyword      = {adolescents,children,metabolic phenotypes,FTO,polymorphism},
  language     = {eng},
  number       = {11},
  pages        = {1730--1735},
  publisher    = {Nature Publishing Group},
  series       = {International Journal of Obesity},
  title        = {Novel genetic variant in FTO influences insulin levels and insulin resistance in severely obese children and adolescents},
  url          = {http://dx.doi.org/10.1038/ijo.2008.168},
  volume       = {32},
  year         = {2008},
}